FI67548C - Foerfarande foer framstaellning av terapeutiskt anvaendbara okahydro-1h-pyrrolo(2,3-g)isokinoliner - Google Patents

Foerfarande foer framstaellning av terapeutiskt anvaendbara okahydro-1h-pyrrolo(2,3-g)isokinoliner Download PDF

Info

Publication number: FI67548C
Authority: FI; Finland
Prior art keywords: alkyl; formula; compound; trans; pyrrolo
Prior art date: 1978-10-13

Application number

FI793183A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI67548B (fi

FI793183A7 (fi

Inventor

Leo Berger

Gary Lee Olson

Original Assignee

Hoffmann La Roche

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1978-10-13

Filing date

1979-10-12

Publication date

1985-04-10

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26754910&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=FI67548(C) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1979-09-10 Priority claimed from US06/073,813 external-priority patent/US4260762A/en

1979-10-12 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1980-04-11 Priority to FI801159A priority Critical patent/FI68833C/fi

1980-04-14 Publication of FI793183A7 publication Critical patent/FI793183A7/fi

1984-12-31 Application granted granted Critical

1984-12-31 Publication of FI67548B publication Critical patent/FI67548B/fi

1985-04-10 Publication of FI67548C publication Critical patent/FI67548C/fi

Links

230000001225 therapeutic effect Effects 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims description 102
125000000217 alkyl group Chemical group 0.000 claims description 67
239000000203 mixture Substances 0.000 claims description 57
238000002360 preparation method Methods 0.000 claims description 29
239000002253 acid Substances 0.000 claims description 28
150000003839 salts Chemical class 0.000 claims description 26
238000000034 method Methods 0.000 claims description 16
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 11
125000003342 alkenyl group Chemical group 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 9
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 8
230000003287 optical effect Effects 0.000 claims description 7
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 claims description 7
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 6
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 5
150000004820 halides Chemical class 0.000 claims description 5
239000002243 precursor Substances 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
239000007858 starting material Substances 0.000 claims description 4
125000000304 alkynyl group Chemical group 0.000 claims description 3
125000001589 carboacyl group Chemical group 0.000 claims description 3
239000003638 chemical reducing agent Substances 0.000 claims description 3
JRVORWMACMEOAD-UHFFFAOYSA-N [N].C1=NC=CC2=CC=CC=C21 Chemical group [N].C1=NC=CC2=CC=CC=C21 JRVORWMACMEOAD-UHFFFAOYSA-N 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 4
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
125000000753 cycloalkyl group Chemical group 0.000 claims 2
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
125000005129 aryl carbonyl group Chemical group 0.000 claims 1
150000002118 epoxides Chemical class 0.000 claims 1
125000002541 furyl group Chemical group 0.000 claims 1
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims 1
229910052757 nitrogen Inorganic materials 0.000 claims 1
125000001544 thienyl group Chemical group 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
238000006243 chemical reaction Methods 0.000 description 49
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 47
239000000243 solution Substances 0.000 description 45
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 42
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
-1 e.g. Chemical group 0.000 description 40
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
239000007787 solid Substances 0.000 description 25
PVKCAQKXTLCSBC-UHFFFAOYSA-N 1h-isoquinolin-4-one Chemical compound C1=CC=C2C(=O)C=NCC2=C1 PVKCAQKXTLCSBC-UHFFFAOYSA-N 0.000 description 18
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
239000002904 solvent Substances 0.000 description 18
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
229960000583 acetic acid Drugs 0.000 description 16
238000010992 reflux Methods 0.000 description 16
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000012267 brine Substances 0.000 description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
239000000908 ammonium hydroxide Substances 0.000 description 13
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
239000000284 extract Substances 0.000 description 13
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
229910000041 hydrogen chloride Inorganic materials 0.000 description 12
238000009835 boiling Methods 0.000 description 11
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
230000000694 effects Effects 0.000 description 10
238000002474 experimental method Methods 0.000 description 10
239000000706 filtrate Substances 0.000 description 10
239000012458 free base Substances 0.000 description 10
239000010410 layer Substances 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000000460 chlorine Substances 0.000 description 9
238000009833 condensation Methods 0.000 description 9
230000005494 condensation Effects 0.000 description 9
239000012043 crude product Substances 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
230000008020 evaporation Effects 0.000 description 9
230000007062 hydrolysis Effects 0.000 description 9
238000006460 hydrolysis reaction Methods 0.000 description 9
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 8
150000001412 amines Chemical class 0.000 description 8
125000005594 diketone group Chemical group 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
241000700159 Rattus Species 0.000 description 7
229910021529 ammonia Inorganic materials 0.000 description 7
239000013256 coordination polymer Substances 0.000 description 7
239000003921 oil Substances 0.000 description 7
235000019198 oils Nutrition 0.000 description 7
239000000047 product Substances 0.000 description 7
KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
239000002585 base Substances 0.000 description 6
229910052744 lithium Inorganic materials 0.000 description 6
230000008018 melting Effects 0.000 description 6
238000002844 melting Methods 0.000 description 6
FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 5
229930040373 Paraformaldehyde Natural products 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
125000004435 hydrogen atom Chemical class [H]* 0.000 description 5
229920002866 paraformaldehyde Polymers 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
239000000126 substance Substances 0.000 description 5
239000011701 zinc Substances 0.000 description 5
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 4
JIHKVQUFCHKYRB-UHFFFAOYSA-N 2-methyl-1,3,4,4a,5,8a-hexahydroisoquinoline-6,8-dione Chemical compound C1C(=O)CC(=O)C2CN(C)CCC21 JIHKVQUFCHKYRB-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
241001061127 Thione Species 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000001035 drying Methods 0.000 description 4
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
QVZMSOCLXCDORR-UHFFFAOYSA-N n-ethyl-3,5-dimethoxy-n-methylaniline;hydrochloride Chemical compound Cl.CCN(C)C1=CC(OC)=CC(OC)=C1 QVZMSOCLXCDORR-UHFFFAOYSA-N 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
235000011181 potassium carbonates Nutrition 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
230000009467 reduction Effects 0.000 description 4
238000006722 reduction reaction Methods 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
238000012360 testing method Methods 0.000 description 4
229910052725 zinc Inorganic materials 0.000 description 4
ZVJBPHMCBRHVEV-XQRVVYSFSA-N (2z)-2-hydroxyiminopentan-3-one Chemical compound CCC(=O)C(\C)=N/O ZVJBPHMCBRHVEV-XQRVVYSFSA-N 0.000 description 3
PMZDQRJGMBOQBF-UHFFFAOYSA-N 1H-quinolin-4-one Natural products C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 3
JFJMWQNUCYLAQW-UHFFFAOYSA-N 2-(3,5-dimethoxycyclohexa-2,5-dien-1-yl)-n-methylethanamine Chemical compound CNCCC1C=C(OC)CC(OC)=C1 JFJMWQNUCYLAQW-UHFFFAOYSA-N 0.000 description 3
OIPARUNOKIPYON-UHFFFAOYSA-N 3-ethyl-2-methyl-1,4a,5,6,7,8,8a,9-octahydropyrrolo[2,3-g]isoquinolin-4-one Chemical compound C1C2CCNCC2C(=O)C2=C1NC(C)=C2CC OIPARUNOKIPYON-UHFFFAOYSA-N 0.000 description 3
DZOKENUNRMDZCS-UHFFFAOYSA-N 3h-isoquinolin-4-one Chemical compound C1=CC=C2C(=O)CN=CC2=C1 DZOKENUNRMDZCS-UHFFFAOYSA-N 0.000 description 3
PYPHDJNEFGUASN-UHFFFAOYSA-N 3h-isoquinoline-4-thione Chemical compound C1=CC=C2C(=S)CN=CC2=C1 PYPHDJNEFGUASN-UHFFFAOYSA-N 0.000 description 3
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
238000006027 Birch reduction reaction Methods 0.000 description 3
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
AWMVMTVKBNGEAK-UHFFFAOYSA-N Styrene oxide Chemical compound C1OC1C1=CC=CC=C1 AWMVMTVKBNGEAK-UHFFFAOYSA-N 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000013078 crystal Substances 0.000 description 3
238000004821 distillation Methods 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000003814 drug Substances 0.000 description 3
230000002964 excitative effect Effects 0.000 description 3
238000001914 filtration Methods 0.000 description 3
229940093915 gynecological organic acid Drugs 0.000 description 3
150000002430 hydrocarbons Chemical group 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
238000006317 isomerization reaction Methods 0.000 description 3
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
VGPBPWRBXBKGRE-UHFFFAOYSA-N n-(oxomethylidene)hydroxylamine Chemical compound ON=C=O VGPBPWRBXBKGRE-UHFFFAOYSA-N 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
235000005985 organic acids Nutrition 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
VSGPVHSTVTXREH-UHFFFAOYSA-N quinolin-4-one Chemical compound C1=CC=C[C]2C(=O)C=CN=C21 VSGPVHSTVTXREH-UHFFFAOYSA-N 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
230000003595 spectral effect Effects 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
VJFARDWQCMLCGT-UHFFFAOYSA-N 1,2,3,4,4a,5-hexahydroisoquinoline Chemical compound C1C=CC=C2CNCCC21 VJFARDWQCMLCGT-UHFFFAOYSA-N 0.000 description 2
BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 2
ORCJWYKSNVSPRX-UHFFFAOYSA-N 1,4a,5,6,7,8,8a,9-octahydropyrrolo[2,3-g]isoquinolin-4-one Chemical compound O=C1C2CNCCC2CC2=C1C=CN2 ORCJWYKSNVSPRX-UHFFFAOYSA-N 0.000 description 2
QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
PVZMYDPRVUCJKV-UHFFFAOYSA-N 3-ethyl-2,6-dimethyl-4a,5,7,8,8a,9-hexahydro-1h-pyrrolo[2,3-g]isoquinolin-4-one Chemical compound C1C2CCN(C)CC2C(=O)C2=C1NC(C)=C2CC PVZMYDPRVUCJKV-UHFFFAOYSA-N 0.000 description 2
GDPDIPLTWCMPIC-UHFFFAOYSA-N 3-ethyl-2-methyl-1,4a,5,6,7,8,8a,9-octahydropyrrolo[2,3-g]isoquinoline-4-thione Chemical compound C1C2CCNCC2C(=S)C2=C1NC(C)=C2CC GDPDIPLTWCMPIC-UHFFFAOYSA-N 0.000 description 2
UEGVVERPSDYMKW-UHFFFAOYSA-N 4h-pyrrolo[2,3-g]isoquinoline Chemical class C1=NC=C2CC3=CC=NC3=CC2=C1 UEGVVERPSDYMKW-UHFFFAOYSA-N 0.000 description 2
JYRADYLOSIMJFK-UHFFFAOYSA-N 6,8-dimethoxy-2-methyl-3,4,4a,7-tetrahydro-1h-isoquinoline Chemical compound C1CN(C)CC2=C(OC)CC(OC)=CC21 JYRADYLOSIMJFK-UHFFFAOYSA-N 0.000 description 2
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
101100178313 Aedes aegypti HP-I gene Proteins 0.000 description 2
241000234282 Allium Species 0.000 description 2
235000002732 Allium cepa var. cepa Nutrition 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
PKXADSMBZJCAGK-UHFFFAOYSA-N Cl.C1=CC=C2C(=O)CN=CC2=C1 Chemical compound Cl.C1=CC=C2C(=O)CN=CC2=C1 PKXADSMBZJCAGK-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
101710094396 Hexon protein Proteins 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
238000006683 Mannich reaction Methods 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
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125000001424 substituent group Chemical group 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
IWOKCMBOJXYDEE-UHFFFAOYSA-N sulfinylmethane Chemical compound C=S=O IWOKCMBOJXYDEE-UHFFFAOYSA-N 0.000 description 1
RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229960001367 tartaric acid Drugs 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
JREYOWJEWZVAOR-UHFFFAOYSA-N triazanium;[3-methylbut-3-enoxy(oxido)phosphoryl] phosphate Chemical compound [NH4+].[NH4+].[NH4+].CC(=C)CCOP([O-])(=O)OP([O-])([O-])=O JREYOWJEWZVAOR-UHFFFAOYSA-N 0.000 description 1
150000003673 urethanes Chemical class 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
238000005406 washing Methods 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
239000004246 zinc acetate Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Medicinal Chemistry (AREA)
Psychiatry (AREA)
Neurology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Biomedical Technology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurosurgery (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

FI793183A 1978-10-13 1979-10-12 Foerfarande foer framstaellning av terapeutiskt anvaendbara okahydro-1h-pyrrolo(2,3-g)isokinoliner FI67548C (fi)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
FI801159A FI68833C (fi)	1979-10-12	1980-04-11	Foerfarande foer framstaellning av terapeutiskt anvaendbara cyloalka(4,5)pyrrolo(2,3-g)isokinoliner

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US95094778A	1978-10-13	1978-10-13
US95094778		1978-10-13
US7381379		1979-09-10
US06/073,813 US4260762A (en)	1979-09-10	1979-09-10	Octahydro-1H-pyrrolo[2,3-g]isoquinolines

Publications (3)

Publication Number	Publication Date
FI793183A7 FI793183A7 (fi)	1980-04-14
FI67548B FI67548B (fi)	1984-12-31
FI67548C true FI67548C (fi)	1985-04-10

Family

ID=26754910

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI793183A FI67548C (fi)	1978-10-13	1979-10-12	Foerfarande foer framstaellning av terapeutiskt anvaendbara okahydro-1h-pyrrolo(2,3-g)isokinoliner

Country Status (18)

Country	Link
EP (1)	EP0010661B1 (cs)
AR (2)	AR228244A1 (cs)
AU (1)	AU528685B2 (cs)
CA (1)	CA1132553A (cs)
CS (1)	CS242858B2 (cs)
DE (1)	DE2967215D1 (cs)
DK (1)	DK430579A (cs)
ES (2)	ES8104806A1 (cs)
FI (1)	FI67548C (cs)
HU (1)	HU181883B (cs)
IE (1)	IE48965B1 (cs)
IL (1)	IL58438A (cs)
MC (1)	MC1285A1 (cs)
NO (1)	NO152873C (cs)
NZ (1)	NZ191830A (cs)
PH (1)	PH14835A (cs)
PT (1)	PT70310A (cs)
SU (3)	SU1109052A3 (cs)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MC1377A1 (fr) *	1980-02-28	1982-01-19	Hoffmann La Roche	Derives d'isoquinoleine
EP0091565B1 (en) *	1982-03-29	1986-04-23	F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft	Process for the manufacture of isoquinoline diones
US4732902A (en) *	1986-05-23	1988-03-22	Hoffmann-La Roche Inc.	Pyrroloisoquinolinyl-dimethyloxoalkyl alkonoates and their use as antipsychotic agents
GB8828669D0 (en) *	1988-12-08	1989-01-11	Lilly Industries Ltd	Organic compounds
JP2002530366A (ja)	1998-11-20	2002-09-17	ビーエーエスエフアクチェンゲゼルシャフト	ビス（オキシム）モノエーテルを製造するための方法および中間体

1979
- 1979-09-27 CA CA336,495A patent/CA1132553A/en not_active Expired
- 1979-10-08 SU SU792819251A patent/SU1109052A3/ru active
- 1979-10-08 SU SU812819251K patent/SU1014474A3/ru active
- 1979-10-10 MC MC791409A patent/MC1285A1/fr unknown
- 1979-10-11 AU AU51697/79A patent/AU528685B2/en not_active Ceased
- 1979-10-11 NZ NZ191830A patent/NZ191830A/en unknown
- 1979-10-11 IL IL58438A patent/IL58438A/xx unknown
- 1979-10-11 EP EP79103908A patent/EP0010661B1/de not_active Expired
- 1979-10-11 DK DK430579A patent/DK430579A/da not_active Application Discontinuation
- 1979-10-11 DE DE7979103908T patent/DE2967215D1/de not_active Expired
- 1979-10-12 NO NO793301A patent/NO152873C/no unknown
- 1979-10-12 FI FI793183A patent/FI67548C/fi not_active IP Right Cessation
- 1979-10-12 IE IE1944/79A patent/IE48965B1/en unknown
- 1979-10-12 HU HU79HO2188A patent/HU181883B/hu not_active IP Right Cessation
- 1979-10-12 CS CS796945A patent/CS242858B2/cs unknown
- 1979-10-12 AR AR278488A patent/AR228244A1/es active
- 1979-10-12 PT PT70310A patent/PT70310A/pt unknown
- 1979-10-12 PH PH23160A patent/PH14835A/en unknown
1980
- 1980-07-02 ES ES493015A patent/ES8104806A1/es not_active Expired
- 1980-07-02 ES ES493014A patent/ES493014A0/es active Granted
1981
- 1981-03-02 SU SU813250198A patent/SU1048985A3/ru active
- 1981-07-02 AR AR285961A patent/AR229096A1/es active

Also Published As

Publication number	Publication date
SU1109052A3 (ru)	1984-08-15
CS694579A2 (en)	1985-08-15
NO152873C (no)	1985-12-04
EP0010661A2 (de)	1980-05-14
EP0010661A3 (en)	1980-10-01
IE48965B1 (en)	1985-06-26
HU181883B (en)	1983-11-28
PT70310A (en)	1979-11-01
IL58438A0 (en)	1980-01-31
ES8104805A1 (es)	1981-05-16
DK430579A (da)	1980-04-14
DE2967215D1 (en)	1984-10-18
IL58438A (en)	1982-12-31
MC1285A1 (fr)	1980-07-22
FI67548B (fi)	1984-12-31
ES493014A0 (es)	1981-05-16
SU1014474A3 (ru)	1983-04-23
CS242858B2 (en)	1986-05-15
AU528685B2 (en)	1983-05-12
AR228244A1 (es)	1983-02-15
ES493015A0 (es)	1981-05-16
ES8104806A1 (es)	1981-05-16
NZ191830A (en)	1984-09-28
SU1048985A3 (ru)	1983-10-15
FI793183A7 (fi)	1980-04-14
PH14835A (en)	1981-12-16
AU5169779A (en)	1980-04-17
NO793301L (no)	1980-04-15
CA1132553A (en)	1982-09-28
EP0010661B1 (de)	1984-09-12
NO152873B (no)	1985-08-26
IE791944L (en)	1980-04-13
AR229096A1 (es)	1983-06-15

Legal Events

Date	Code	Title	Description
2004-08-31	MM	Patent lapsed	Owner name: F HOFFMANN-LA ROCHE & CO

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FI84827C (fi)	1992-01-27	Foerfarande foer framstaellning av terapeutiskt anvaendbara pyridinderivat.
KR20250152103A (ko)	2025-10-22	질환 또는 장애 치료용 하이드로퀴나졸린 유도체
US3816422A (en)	1974-06-11	2,3-dihydro-oxo-imidazo(1,2-a)pyrimidines and salts thereof
FI67548B (fi)	1984-12-31	Foerfarande foer framstaellning av terapeutiskt anvaendbara okahydro-1h-pyrrolo(2,3-g)isokinoliner
EP2427460B1 (en)	2014-03-26	Novel isoquinoline derivatives
US4260762A (en)	1981-04-07	Octahydro-1H-pyrrolo[2,3-g]isoquinolines
US9156812B2 (en)	2015-10-13	Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine
US11286233B2 (en)	2022-03-29	Stilbene derivatives for the treatment of CNS and other disorders
FI68833B (fi)	1985-07-31	Foerfarande foer framstaellning av terapeutiskt anvaendbara cykoalka(4,5)pyrrolo(2,3-g)isokinoliner
US4388467A (en)	1983-06-14	Cycloalka[4,5]pyrrolo[2,3-g]isoquinolines
Weis et al.	2003	Synthesis of new analogues of diphenylpyraline
CN105367472A (zh)	2016-03-02	吲哚啉类衍生物及其在药物上的应用
CA1160228A (en)	1984-01-10	Cycloalka¬4,5\|pyrrolo¬2,3-g\|isoquinolines
RU2783521C1 (ru)	2022-11-14	Ингибиторы цитохрома 11В2 человека
CS242900B2 (cs)	1986-05-15	Způsob výroby oktahydro-1H-pyrroio[2,3-g]isochinolinů
KR850000032B1 (ko)	1985-02-13	사이클로알카[4,5] 피롤로[2,3-g] 이소퀴놀린의 제조방법
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EP0375536A1 (en)	1990-06-27	Derivatives of 1,7'-(imidazo-(1,2-a)pyridine) 5'-(6'H) ones and process for their preparation
HU199462B (en)	1990-02-28	Process for producing pyrimido/4,5-a/quinoline derivatives and pharmaceutical compositions comprising same